Intrahypothalamic secretion of angiotensin II in response to immunological or non-immunological stress in rats : a microdialysis study

我们以前报道过脑血管紧张素II （ANG II）受体参与大鼠免疫或非免疫应激引起的发热。本研究采用微透析技术研究免疫[前列腺素E_2 （PGE_2）注射]或非免疫（固定化）应激对大鼠下丘脑分泌ANG II的影响。我们的微透析研究（灌注流速为2 μl/min，回收率为14.2%）表明，PGE_2 （2 μg/2 μl灌注液/min）在下丘脑内灌注时，可以通过灌注液中存在少量的ANG II（平均0.17 pg/2 μl灌注液/min， n=3）来检测下丘脑中ANG II的释放。在车辆输注过程中，ANG II未发生这种释放（n=4）。因此，我们有理由认为，下丘脑中的PGE_2与下丘脑内PGE受体结合，导致ANG II释放。随后，下丘脑内释放的ANG II可能调节pge_2诱导的发热反应。相比之下，当大鼠暴露于固定应激时，大鼠下丘脑未检测到ANG II的分泌。由于本研究使用的微透析探针回收率为14.2%，且肽极不稳定，可能无法测量实际分泌的ANG II。为了检测如此少量的肽，技术改进是必要的，例如，通过使用使肽失活的酶抑制剂。

We previously reported that brain angiotensin II (ANG II) receptors contribute to the fever induced by immunological or non-immunological stress in rats. The present study was carried out to investigate whether immunological [prostaglandin E_2 (PGE_2) injection] or non-immunological (immobilization) stress elicits the secretion of ANG II in the hypothalamus in rats, using microdialysis technique. Our microdialysis study (perfusion flow rate=2 μl/min and recovery rate=14.2%) showed that, during intrahypothalamic perfusion with PGE_2 (2 μg/2 μl perfusate/min), ANG II release in the hypothalamus could be detected by the presence of a small amount of ANG II in the perfusate (on average, 0.17 pg/2 μl perfusate/min ; n=3). Such a release of ANG II did not occur during vehicle infusion (n=4). It is therefore reasonable to consider that PGE_2 in the hypothalamus binds to intrahypothalamic PGE receptors, which results in ANG II release. Subsequently, ANG II released within the hypothalamus might modulate the PGE_2-induced febrile responses. In contrast, when rats were exposed to immobilization stress, no secretion of ANG II was detected in the rat's hypothalamus. Since the recovery rate of the microdialysis probe used in this study was 14.2% and the peptide is so unstable, actual secretion of ANG II might have been unable to be measured. Technical improvement is necessary to detect such a small amount of the peptide, for example by using the inhibitors of the enzyme which inactivates the peptide.